Interferons are a family of proteins whose synthesis can be induced in various vertebrate cells by treatment with any of a large variety of inducers. The interferons are released from the producing cells, they are bound to specific cell surface receptors on other cells and alter various characteristics of these cells. We have isolated in the past several cDNA clones that specify mRNAs whose levels are increased in cells exposed to interferons. We are continuing our studies on the mechanisms of gene activation by interferons. We are planning: a) to clone various genes activated by various interferons, b) to determine if the increase in the level of particular mRNAs is a consequence of an increased frequency of transcription or a decreased rate of turnover or both, c) to establish the locations and sequences of DNA segments making the expression of particular genes responsive to particular interferons, d) to attempt to identify and characterize trans-acting elements mediating the activation of particular genes by interferons, e) to test the function of proteins (which are specified by the cloned genes) by transfection. We have characterized in the past various enzymes and other proteins that are induced by interferons. Some of these were found to be located primarily in the nuclear fraction of the cell extract. We are planning: a) to purify and characterize a "nuclear" (2'-5')(A)n synthetase and study the reaction it catalyzes, b) to attempt to generate antibodies to the "nuclear" (2'-5')(A)n synthetase for studies on I) the subcellular localization of the enzyme, II) its relatedness (if any) to the cytoplasmic (2'-5')(A)n synthetase and III) the nature of the nucleic acid to which it is bound, and c) to identify further nuclear proteins induced by interferons and to test these for binding to double stranded RNA, (2'-5')(A)n, and GDP.